Methylation signatures as biomarkers for non-invasive early detection of breast cancer: A systematic review of the literature.

BACKGROUND: Early detection of breast cancer would help alleviate the burden of treatment for early-stage breast cancer and help patient prognosis. There is currently no established gene panel that utilizes the potential of DNA methylation as a molecular signature for the early detection of breast cancer. This systematic review aims to identify the optimal methylation biomarkers for a non-invasive liquid biopsy assay and the gaps in knowledge regarding biomarkers for early detection of breast cancer. METHODS: Following the PRISMA-ScR method, Pubmed and Google Scholar was searched for publications related to methylation biomarkers in breast cancer over a five-year period. Eligible publications were mined for key data fields such as study aims, cohort demographics, types of breast cancer studied, technologies used, and outcomes. Data was analyzed to address the objectives of the review. RESULTS: Literature search identified 112 studies of which based on eligibility criteria, 13 studies were included. 28 potential methylation gene targets were identified, of which 23 were methylated at the promoter region, 1 was methylated in the body of the gene and 4 were methylated at yet to be identified locations. CONCLUSIONS: Our evaluation shows that at minimum APC, RASSFI, and FOXA1 genes would be a promising set of genes to start with for the early detection of breast cancer, based on the sensitivity and specificity outlined in the studies. Prospective studies are needed to optimize biomarkers for broader impact in early detection of breast cancer.

The Influence of Linguistic Agency and Causality Attribution in Support-seeking about Depression on Perceived Stigma and Support Messages.

This experiment examined how two language features-linguistic agency and assignment of causality-of online support-seekers' messages regarding depression influenced viewers' perceived stigma and features of their support messages. Participants (N = 254) read and responded to an online support-seeking post about depression. Our results revealed that personal stigma toward a depressed individual was lower when the individual disclosed a biological cause for the depression and assigned agency to depression than agency to human. Additionally, when agency was assigned to depression with a biological rather than non-biological cause, more positive emotion words were utilized in participants' response posts. Cognitive process words were used more often in response to messages with non-biological causality than biological causality.

Health-related quality of life in adolescents with or at risk for type 2 diabetes mellitus.

OBJECTIVE: To evaluate how adolescents with or at risk for type 2 diabetes mellitus (T2DM) and their parent/guardians (parents) perceive adolescents' health-related quality of life. STUDY DESIGN: We interviewed overweight/obese, 12- to 18-year-old youth with T2DM, prediabetes, or insulin resistance and one parent from 5 US sites. Assessments included Pediatric Quality of Life Inventory (PedsQL), Health Utilities Index, family conflict, and diabetes burden. RESULTS: In 108 adolescents, diagnoses included 40.7% with T2DM, 25.0% with prediabetes, and 34.3% with insulin resistance. PedsQL summary score (SS) was higher in adolescents than parents (P=.02). Parents rated physical functioning lower than adolescents (P<.0001), but there were no differences in psychosocial health. Adolescent PedsQL SS did not differ with diagnosis, but was inversely associated with adolescent body mass index z-score (P=.0004) and family conflict (P<.0001) and associated with race/ethnicity (P<.0001). Number of adolescent co-morbidities (P=.007) and burden of diabetes care (P<.05) were inversely associated with parent PedsQL SS. There were no differences in the Health Utilities Index-Mark 3 multi-attribute utility score. CONCLUSIONS: Parents perceive their adolescents' physical functioning as more impaired than adolescents themselves. Contextual factors including severity of obesity, race/ethnicity, family conflict, and burden of diabetes care influence health-related quality of life. Family-based approaches to treatment and prevention of T2DM may benefit from increased attention to the biopsychosocial context.

Ricin induces IL-8 secretion from human monocyte/macrophages by activating the p38 MAP kinase pathway.

Polymorphonuclear cell (PMN) infiltration is a hallmark of ricin-induced mucosal inflammation, yet the cellular processes involved in initiating this reaction remain undefined. In this study we report that ricin stimulates the human monocyte/macrophages cell line 28SC to secrete IL-8, a potent PMN chemoattractant. IL-8 release in response to ricin was both dose- and time-dependent. 28SC cells did not secrete IL-8 when exposed to formaldehyde-inactivated holotoxin or ricin B subunit. Furthermore, IL-8 induction could be blocked by brefeldin A, which inhibits ricin translocation into the cytosol. As predicted from the literature, we observed elevated levels of p38 mitogen activated protein kinase (MAPK), a post-transcriptional regulator of IL-8, in 28SC cells as early as 3h after ricin exposure. Treatment of 28SC cells with the pyridylimidizole analogue SB203580, a known inhibitor of p38 MAPK, suppressed ricin-mediated IL-8 release. We conclude that ricin stimulates human monocyte/macrophages to produce IL-8 by activation of the p38 MAPK pathway, raising the possibility that p38 MAPK inhibitors may potentially serve as therapeutic agents to suppress mucosal inflammation associated with ricin intoxication.